Journal article
Phenformin Promotes Keratinocyte Differentiation via the Calcineurin/NFAT Pathway.
- Zhou Q Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China; Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China; Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China.
- Kim SH Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- Pérez-Lorenzo R Department of Dermatology, Columbia University Medical Center, New York, New York, USA.
- Liu C Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China; Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.
- Huang M Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, USA.
- Dotto GP Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
- Zheng B Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- Wu X Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China; Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China; Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: xunwei_2006@hotmail.com.
- 2020-07-04
Published in:
- The Journal of investigative dermatology. - 2020
English
Phenformin is a drug in the biguanide class that was previously used to treat type 2 diabetes. We have reported the antitumor activities of phenformin to enhance the efficacy of BRAF-MAPK kinase-extracellular signal-regulated kinase pathway inhibition and to inhibit myeloid-derived suppressor cells in various melanoma models. Here we demonstrate that phenformin suppresses tumor growth and promotes keratinocyte differentiation in the 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate two-stage skin carcinogenesis mouse model. Moreover, phenformin enhances the suspension-induced differentiation of mouse and human keratinocytes. Mechanistically, phenformin induces the nuclear translocation of NFATc1 in keratinocytes in an AMPK-dependent manner. Pharmacologic or genetic inhibition of calcineurin and NFAT signaling reverses the effects of phenformin on keratinocyte differentiation. Taken together, our study reveals an antitumor activity of phenformin to promote keratinocyte differentiation that warrants future translational efforts to repurpose phenformin for the treatment of cutaneous squamous cell carcinomas.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1016/j.jid.2020.05.114
- PMID 32619504
- Persistent URL
- https://sonar.ch/global/documents/186381
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